Non-Typeable Haemophilus influenzae Invade Choroid Plexus Epithelial Cells in a Polar Fashion
Christian Wegele1, Carolin Stump-Guthier1, Selina Moroniak1
1Pediatric Infectious Diseases, Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
Abstract:
Non-typeable Haemophilus influenzae (NTHI) is a pathogen of the human respiratory tract causing the majority of invasive H. influenzae infections. Severe invasive infections such as septicemia and meningitis occur rarely, but the lack of a protecting vaccine and the increasing antibiotic resistance of NTHI impede treatment and emphasize its relevance as a potential meningitis causing pathogen. Meningitis results from pathogens crossing blood-brain barriers and invading the immune privileged central nervous system (CNS). In this study, we addressed the potential of NTHI to enter the brain by invading cells of the choroid plexus (CP) prior to meningeal inflammation to enlighten NTHI pathophysiological mechanisms. A cell culture model of human CP epithelial cells, which form the blood-cerebrospinal fluid barrier (BCSFB) in vivo, was used to analyze adhesion and invasion by immunofluorescence and electron microscopy. NTHI invade CP cells in vitro in a polar fashion from the blood-facing side. Furthermore, NTHI invasion rates are increased compared to encapsulated HiB and HiF strains. Fimbriae occurrence attenuated adhesion and invasion. Thus, our findings underline the role of the BCSFB as a potential entry port for NTHI into the brain and provide strong evidence for a function of the CP during NTHI invasion into the CNS during the course of meningitis.
Insights
Non-typeable Haemophilus influenzae (NTHI) can invade the brain by crossing the blood-cerebrospinal fluid barrier. This study shows NTHI enters choroid plexus cells, highlighting a potential pathway for meningitis.
Area of Science:
- Microbiology
- Infectious Diseases
- Neuroscience
Background:
- Non-typeable Haemophilus influenzae (NTHI) is a significant respiratory pathogen.
- NTHI causes invasive infections, and increasing antibiotic resistance complicates treatment.
- Meningitis involves pathogens breaching the blood-brain barrier to enter the central nervous system (CNS).
Purpose of the Study:
- To investigate NTHI's potential to invade the brain via choroid plexus (CP) epithelial cells.
- To elucidate NTHI's pathophysiological mechanisms in entering the CNS.
- To understand the role of the blood-cerebrospinal fluid barrier (BCSFB) in NTHI meningitis.
Main Methods:
- Utilized a human CP epithelial cell culture model representing the BCSFB.
- Analyzed NTHI adhesion and invasion using immunofluorescence and electron microscopy.
- Compared invasion rates of NTHI with encapsulated Haemophilus influenzae strains (HiB, HiF).
Main Results:
- NTHI demonstrated polar invasion into CP cells from the blood-facing side.
- NTHI exhibited higher invasion rates compared to encapsulated HiB and HiF strains.
- Fimbriae presence was found to attenuate NTHI adhesion and invasion.
Conclusions:
- The BCSFB, formed by CP cells, serves as a potential entry point for NTHI into the brain.
- CP cells play a crucial role in NTHI's invasion of the CNS during meningitis.
- Findings provide evidence for NTHI's mechanism of CNS entry, relevant for meningitis pathogenesis.
